Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:
NCT00063635
First received: July 1, 2003
Last updated: August 27, 2012
Last verified: August 2012
  Purpose

The purpose of this study is to determine if therapeutic modification of insulin resistance or oxidative stress leads to improvement in serum or histologic indicators of liver injury or quality of life.


Condition Intervention Phase
Fatty Liver
Drug: Metformin
Dietary Supplement: Vitamin E
Drug: Matching placebo
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator)
Primary Purpose: Treatment
Official Title: Clinical Research Network in Nonalcoholic Steatohepatitis: Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC)

Resource links provided by NLM:


Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:
  • Number of Participants With Sustained Reduction in Alanine Aminotransferase (ALT) to Either 50% of Baseline Value or < 40 IU/L [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    The primary outcome was sustained reduction in ALT level, defined as 50% or less of the baseline level or 40 IU/L or less at each visit from 48 to 96 weeks of treatment.


Secondary Outcome Measures:
  • Change in Serum Aspartate Aminotransferase (AST) [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
  • Change in Nonalcoholic Fatty Liver Disease (NAFLD) Score (Histologic Feature Scores Determined by Standardized Scoring of Liver Biopsies) From Baseline at 96 Weeks of Treatment [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Histological activity was assessed using the NAFLD activity score on a scale of 0 to 8, with higher scores indicating more severe disease; the components of this measure include steatosis (0-3), lobular inflammation (0-3), and hepatocellular ballooning (0-2).

  • Number of Participants With Improvement in Liver Fibrosis Score [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Fibrosis is assessed on a scale of 0 to 4 with higher scores indicating more severe fibrosis. This secondary outcome measure is the number of participants that experienced a decrease in fibrosis score at 96 weeks compared to baseline, which indicates improvement in fibrosis.

  • Number of Participants With Improvement in Steatosis Score [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Steatosis is assessed on a scale of 0 to 3 with higher scores indicating more severe steatosis. This secondary outcome measure is the number of participants that experienced a decrease in steatosis score at 96 weeks compared to baseline, which indicates improvement in steatosis.

  • Number of Participants With Improvement in Lobular Inflammation Score [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Lobular inflammation is assessed on a scale of 0 to 3 with higher scores indicating more severe lobular inflammation. This secondary outcome measure is the number of participants that experienced a decrease in lobular inflammation score at 96 weeks compared to baseline, which indicates improvement in lobular inflammation.

  • Number of Participants With Improvement in Ballooning Degradation Score [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Ballooning is assessed on a scale of 0 to 2 with higher scores indicating more severe ballooning. This secondary outcome measure is the number of participants that experienced a decrease in ballooning score at 96 weeks compared to baseline, which indicates improvement in ballooning.

  • Change in Body Mass Index [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
  • Change in Serum Vitamin E Levels [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Change in alpha-Tocopherol

  • Change in Quality of Life (QOL) Scores- Physical Health [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Change in self-reported QOL physical health Pediatric Quality of Life Inventory (version 4.0) scores were recorded to range from 0 to 100 with increasing scores indicating better quality of life.

  • Change in QOL- Psychosocial Health [ Time Frame: baseline and 96 weeks ] [ Designated as safety issue: No ]
    Change in self-reported QOL physical health Pediatric Quality of Life Inventory (version 4.0) scores were recorded to range from 0 to 100 with increasing scores indicating better quality of life.


Enrollment: 173
Study Start Date: September 2005
Study Completion Date: February 2010
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: 1
Metformin, 500 mg, twice daily
Drug: Metformin
500 mg, twice daily
Active Comparator: 2
Vitamin E, 400 IU, twice daily
Dietary Supplement: Vitamin E
400 IU, twice daily
Other Name: Nature Made
Placebo Comparator: 3
Matching placebo
Drug: Matching placebo
Twice daily

  Eligibility

Ages Eligible for Study:   8 Years to 17 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria
  • Age 8-17 years at first screening visit
  • Histologic evidence of Nonalcoholic Fatty Liver Disease (NAFLD) - biopsy cannot be older than 6 months as of randomization
  • ALT level >60 U/L at time of screening and on one previous occasion determined at least one month but no greater than 6 months prior to screening ALT
  • Consent
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00063635

Locations
United States, California
University of California, San Diego
San Diego, California, United States, 92103
University of California, San Francisco
San Francisco, California, United States, 94143
United States, District of Columbia
Children's National Medical Center
Washington, District of Columbia, United States, 20010
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Maryland
Johns Hopkins University
Baltimore, Maryland, United States, 21205
United States, Missouri
St. Louis University
St. Louis, Missouri, United States, 63110
United States, Ohio
Case Western Reserve University
Cleveland, Ohio, United States, 44109
United States, Texas
Texas Children's Hospital
Houston, Texas, United States, 77030
United States, Virginia
Virginia Commonwealth University
Richmond, Virginia, United States, 23298
United States, Washington
University of Washington
Seattle, Washington, United States, 98195
Sponsors and Collaborators
  More Information

Additional Information:
No publications provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier: NCT00063635     History of Changes
Other Study ID Numbers: NASH - PEDIATRICS (IND)
Study First Received: July 1, 2003
Results First Received: June 26, 2012
Last Updated: August 27, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):
Non alcoholic fatty liver disease

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Metformin
Vitamin E
Alpha-Tocopherol
Tocopherols
Tocotrienols
Vitamins
Hypoglycemic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Micronutrients
Growth Substances

ClinicalTrials.gov processed this record on July 23, 2014